Our objective is to study placental angiogenesis (development of the placental blood supply). Because the mammalian placenta is the organ through which nutrients and wastes are exchanged between the maternal and fetal systems, the size of the placental blood supply has a profound influence on the rate of fetal nutrient uptakes, and thereby on the rate of fetal growth. Factors affecting fetal development, in turn, have a dramatic effect on birth weight, which is the major determinant of survival and growth after birth. Recent techniques for altering the genetic makeup of embryos necessitate an understanding of factors that affect the subsequent growth and development of those embryos. The research will focus on determining the ontogeny of placental production of angiogenic factors throughout pregnancy (experiments 1 and 2). The role of angiogenic factors in establishing an adequate placental blood supply and in survival and growth of fetuses will be evaluated. In experiment 3, uterine space available for placental formation will be reduced to induce compensatory growth of the placenta and determine the relationships between placental compensatory growth and angiogenesis. Placental angiogenic activity will be tested by using two in vitro bioassays, as well as an in vivo bioassay, so that the ability of placental angiogenic factors to stimulate all aspects of angiogenesis can be confirmed. The ability preparations obtained from placenta to induce angiogenesis in nonpregnant uteri will be tested in experiment 4.